Celldex Therapeutics, Inc. · NASDAQ:CLDX
Celldex Therapeutics — Technical Presentation (November 2013)
31 slides from Celldex Therapeutics's technical presentation, Nov 25, 2013
Slide 1: Rindopepimut Society for Neuro-Oncology (SNO) 2014 Update
Rindopepimut Society for Neuro-Oncology (SNO) 2014 Update November 25, 2013
Slide 2: Forward Looking Statement
Forward Looking Statement This communication contains "forward-looking" statements within the meaning of the Private Securities Litigation Reform Act of 1995. All statements other than statements of historical fact are statements that could be forward-looking statements. You can identify these forwa
Slide 3: Rindopepimut: A Phase 3 Immunotherapy Targeting EGFRvIII-expressing Glioblastoma
Rindopepimut: A Phase 3 Immunotherapy Targeting EGFRvIII-expressing Glioblastoma • Rindopepimut is the only vaccine in development targeting EGFRvIII (v3) • EGFRvIII – Highly tumor specific, expressed only in tumors not normal tissues – Target has been validated, gaining importance as a tumor marker
Slide 4: EGFR Mutation Variant III (EGFRvIII)
EGFR Mutation Variant III (EGFRvIII) • Tumor-specific oncogene expressed in one-third of primary GBM, seldom expressed with IDH mutations but not in normal tissue • EGFRvIII(+) cells may induce growth in EGFRvIII(-) cells via paracrine signaling, membrane-derived microvesicles and tumor stem cells1-
Slide 5: Biology Supports Clinical Benefit
Biology Supports Clinical Benefit Rindo eliminates vIII from tumor cells Induction of potent immune response to EGFRvIII • 85% of patients developed significant anti- EGFRvIII antibody titers which increased with time on study • Majority (67%) developed titers above 1:12,800 • Anti-EGFRvIII titers m
Slide 6: Rationale for Rindopepimut Plus Bevacizumab in Recurrent GBM
Rationale for Rindopepimut Plus Bevacizumab in Recurrent GBM • Compassionate use evidence suggest that rindopepimut may induce specific immune responses and regression in multifocal and bulky tumors – Marked tumor regression with rindopepimut in combination with standard treatments – Central review
Slide 7: Phase II ReACT Study Design
Phase II ReACT Study Design ——— ReA@T Rindopepimut / GM-CSF + mn Clinica study of rindopepimut in Group 1 Bevacizumab relapsed EGFRulll positive glioblastoma Cereal Randomization (1:1) (n=70) Control (KLH) + Bevacizumab Group 2: Group 2C (Confirmatory): Bevacizumab refractory (n= 25) Rindopepimut /
Slide 8: Phase II ReACT Study Design cont.
Phase 2 ReACT Study Design cont. Eligibility • 1st or 2nd relapse of GBM • EGFRvIII+ (as per centralized IDE-approved RT-PCR assay) • Prior conventional radiation and temozolomide • No radiation within 3 months of entry • Systemic corticosteroid therapy = 4 mg of dexamethasone daily • No metastatic
Slide 9: ReACT Study Status
ReACT Study Status Bevacizumab-naïve • Interim results available for the 1st 40 patients – 12 patients continue to receive treatment – A total of 27 patients continue to be followed for survival Bevacizumab-refractory • Enrollment to initial cohort is complete; 25 patients treated – 1 patient contin
Slide 10: Patient Characteristics
Patient Characteristics 10 Bevacizumab Refractory (n=25) Bevacizumab Naïve Rindopepimut + Bevacizumab (n=20) Control (KLH) + Bevacizumab (n=20) Age, years (median [range]) =50 years (n [%]) 58 (39-79) 20 (80%) 60 (51-79) 20 (100%) 56 (30-75) 15 (75%) Male (n [%]) 16 (64%) 9 (45%) 11 (55%) KPS (n [%]
Slide 11: Group 1: Bevacizumab-Naive Recurrent GBM
Group 1: Bevacizumab-Naive Recurrent GBM
Slide 12: Overall and Progression-Free Survival Bevacizumab-Naïve Recurrent GBM – Interim Data
Months Overall Survival (%) 0 2 4 6 8 10 12 14 16 18 20 0 25 50 75 100 Progression-Free Survival (%) HR = 0.74 (0.34, 1.61) p = 0.47 12 Overall and Progression-Free Survival Bevacizumab-Naïve Recurrent GBM – Interim Data HR = 0.43 (0.13, 1.44) p = 0.16 Median follow-up: 6.4 months for rindopepimut 5
Slide 13: First Controlled Data for EGFRvIII Supports that EGFRvIII Patients Fare Worse
First Controlled Data for EGFRvIII Supports that EGFRvIII Patients Fare Worse than the General GBM population Median OS, Months Median PFS, Months Bevacizumab only (AVF3708g, all comers) 9.3 4.2 Bevacizumab only (ReACT Control , EGFRvIII only) 7.9 2.0 13
Slide 14: Early Anti-EGFRvIII Response Correlates with Survival in Recurrent GBM
14 Early Anti-EGFRvIII Response Correlates with Survival in Recurrent GBM Treated with Rindopepimut + Bevacizumab Bevacizumab-Naïve * Based on the generation of anti-EGFRvIII antibody titer = 1:12,800 by Day 57. Similar results observed at Day 29 as well as across a range of cut-off values (1:800 to
Slide 15: Tumor Shrinkage: Bevacizumab-Naïve Recurrent GBM
Tumor Shrinkage: Bevacizumab-Naïve Recurrent GBM 15 > PD PR Maximum Shrinkage of Target Lesions 15 Control + Bevacizumab Rindopepimut + Bevacizumab -100% -75% -50% -25% 0% 25% 50% 75% 100%
Slide 16: Preliminary Analysis of Anti-Tumor Effect Bevacizumab-Naïve Recurrent GBM
16 Preliminary Analysis of Anti-Tumor Effect Bevacizumab-Naïve Recurrent GBM ** Two additional patients receiving rindopepimut+bev and one patient receiving control+bev have experienced >50% shrinkage by either investigator or expert panel review, and are pending followup for confirmation of respons
Slide 17: Progression-Free and Overall Survival Bevacizumab-Refractory Recurrent GBM
Progression-Free and Overall Survival Bevacizumab-Refractory Recurrent GBM 18 PFS based on Investigator Review Median follow-up: 10.0 months Median, Months (95% Cl) 6-Month Rate Overall Survival 5.6 (3.2, 6.7) 48% Progression-free Survival 1.9 (1.8, 2.8) 8%
Slide 18: Early Anti-EGFRvIII Response Correlates with Survival, Bevacizumab-Refractory
Overall Survival (%) 19 Early Anti-EGFRvIII Response Correlates with Survival in Recurrent GBM Treated with Rindopepimut + Bevacizumab Bevacizumab-Refractory * Based on the generation of anti-EGFRvIII antibody titer = 1:12,800 by Day 57. Similar results observed at Day 29 as well as across a range o
Slide 19: Tumor Shrinkage Bevacizumab-Refractory Recurrent GBM
Tumor Shrinkage Bevacizumab-Refractory Recurrent GBM PD PR * * 20 Maximum Shrinkage of Target Lesions Data from Investigator Read * Previously treated with bevacizumab but did not have progression within 2 months of discontinuation. > -100% -75% -50% -25% 0% 25% 50% 75% 100% 125% 150% 175% 200%
Slide 20: Anti-Tumor Effect Bevacizumab-Refractory Recurrent GBM
Anti-Tumor Effect Bevacizumab-Refractory Recurrent GBM • ITT analysis of primary endpoint: 2/25 (8%) patients receiving rindopepimut + bevacizumab were progression-free at 6 months – Study designed with an ambitious goal of PFS6=20% – No comparative data available to define expected outcome for EGFR
Slide 21: Anti-Tumor Effect Bevacizumab-Refractory Recurrent GBM
1. One ongoing Partial Response (-79% shrinkage in measurable disease) by Investigator assessment; deemed Stable Disease due to lack of clearly measurable disease by expert panel • Patient continues treatment at 8.3 months • Prior treatments: partial resection, radiation and temozolomide with progre
Slide 22: Tumor Response in Bevacizumab-Refractory Recurrent GBM
63 yr, female with PD after XRT/TMZ and 7 cycles of adjuvant TMZ; then 2nd PD after 3.5 months on BEV monotherapy Pre-Rindopepimut Ongoing response after 5 cycles of Rindopepimut + BEV Patient continues to be progression free, currently at 8+ months of treatment with rindopepimut + BEV Tumor Respons
Slide 23: Anti-Tumor Effect Bevacizumab-Refractory Recurrent GBM cont.
Anti-Tumor Effect Bevacizumab-Refractory Recurrent GBM cont. 3. One Complete Response (9.3 months duration) by Investigator assessment; deemed Stable Disease due to lack of clearly measurable disease by expert panel • Patient experienced progression-free survival of 11 months • Prior treatments: Gro
Slide 24: Q&A Celldex Therapeutics
Q&% Celldex therapeutics
Slide 25: Safety: Bevacizumab-Refractory and Bevacizumab-Naïve Recurrent GBM
Safety: Bevacizumab-Refractory and Bevacizumab-Naïve Recurrent GBM • Rindopepimut plus bevacizumab (dosing for up to 13 months) has been well-tolerated – No unexpected toxicity associated with concomitant bevacizumab administration – No treatment-related toxicity resulting in discontinuation of stud
Slide 26: ReACT Conclusions
ReACT Conclusions • Rindopepimut combined with bevacizumab was very well tolerated • Remarkable frequency and level of anti-EGFRvIII immune responses were generated despite prior chemotherapy and growing tumor • Encouraging tumor response and survival data – 48% OS rate at 6 months in refractory pat
Slide 27: Additional Updates
Additional Updates
Slide 28: Rindopepimut: Long-Term Follow-up from Phase 2 Trials in de novo GBM
Rindopepimut: Long-Term Follow-up from Phase 2 Trials in de novo GBM Overall Survival (%) • Three Phase 2 Studies: ACTIVATE (n=18), ACT II (n = 22), ACT III (n=65) . Newly diagnosed, resected, EGFRvIII-expressing GBM • Significant anti-EGFRvIII immunity in 85% of ACT III patients (67% > 1:12,800) •
Slide 29: ACT IV: Phase 3 Study in Newly-Diagnosed EGFRvIII-positive Glioblastoma
ACT IV: Phase 3 Study in Newly-Diagnosed EGFRvIII-positive Glioblastoma • Randomized (1:1), double-blind, placebo controlled study in up to 450 patients with newly diagnosed, surgically resected, EGFRvIII-positive glioblastoma (including 374 patients with minimal residual disease) (adaptive design);
Slide 30: ACT IV Status Update
ACT IV Status Update • In this adaptive design study, total accrual is dependent on the following variables: – Overall enrollment rate – Patients with minimal residual disease – Rate of events (deaths) • 351 patients have been randomized to date • Due to event rate and patient mix, enrollment will e
Slide 31: Q&A Celldex Therapeutics
Q&% Celldex therapeutics
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